Process for producing mouldings

ABSTRACT

A novel process for producing mouldings, especially contact lenses, is described, comprising the following steps: a) introducing into a mould a prepolymer containing photo crosslinkable groups that is liquid at room temperature or is readily meltable and is substantially free of solvents; b) initiating the photo cross-linking for a period of &lt;20 minutes; c) opening the mould, so that the moulding can be removed for the mould. In accordance with the process according to the invention, it is possible especially to produce contact lenses having valuable properties.

The invention relates to a novel process for producing mouldings,especially opthalmological mouldings, such as especially contact lenses,in which a liquid or readily meltable prepolymer containingcrosslinkable groups is crosslinked in the absence of solvents, and tothe further processing thereof to form ready-to-use contact lenses.

Processes for producing mouldings, especially contact lenses, bysuitable crosslinking of polymers containing crosslinkable groups areknown. The previously known processes are customarily carried out in thepresence of a solvent and optionally with the addition of vinylcomonomers. For the production of a ready-to-use contact lens it isaccordingly often necessary to replace the solvent when the crosslinkingis complete and/or to extract unreacted monomers. There is therefore aneed for a simplified process for producing mouldings that can becarried out without solvent and does not include an extraction step.

The present Application therefore relates to a process for producingmouldings that comprises the following steps:

a) introducing into a mould a prepolymer containing photocrosslinkablegroups that is liquid at room temperature or is readily meltable and issubstantially free of solvents,

b) initiating the photocrosslinking for a period of <20 minutes,

c) opening the mould, so that the moulding can be removed from themould.

The criterion that the prepolymer be liquid or readily meltable is to beunderstood according to the invention as meaning that the prepolymer isliquid at room temperature or has a melting point of ≦100° C.,preferably ≦75° C. and especially ≦50° C. Preferred for the processaccording to the invention are prepolymers that are liquid at roomtemperature.

The polymeric base structure of the prepolymers can belong to a widevariety of classes of polymer; examples are polyethers, polyesters,polyureas, polyurethanes, polycarbonates and polyamides. Also possibleare homogeneous mixtures of two or more different polymers.

When the prepolymer is a polyether, then, for example, a polyalkyleneglycol homo- or co-polymer or a polytetrahydrofuran comes intoconsideration. Examples of suitable polyalkylene glycol homo- orco-polymers are C₁-C₆polyalkylene glycol homopolymers or blockcopolymers and preferably polymers based on polyethylene glycol orpolypropylene glycol or polyethylene glycol/polypropylene glycol blockcopolymers.

Preference is given to the use of a polyester, polyamide, polyamide withpolyethylene glycol blocks, polyurethane, polyurea or of one of theabove-mentioned polyethers as prepolymer.

The prepolymer used according to the invention must also containphotocrosslinkable groups. Photocrosslinkable groups are to beunderstood as being customary photocrosslinkable groups well known tothe person skilled in the art, especially those such as have alreadybeen proposed for the production of contact lens materials. They includeespecially, but not exclusively, groups containing carbon-carbon doublebonds. In order to demonstrate the wide variety of suitablecrosslinkable groups, there may be mentioned here as crosslinkingmechanisms, merely by way of example, radical polymerisation,2+2-cycloaddition, Diels-Alder reaction, ROMP (Ring Opening MetathesisPolymerisation), vulcanisation, cationic crosslinking and epoxy curing.Suitable photopolymerisable groups are especially radically orcationically polymerisable groups.

Suitable radically crosslinkable groups correspond, for example, toformula

P₁—(Y)_(m)—(R—X)_(p)—  (1),

wherein

P₁ is a radically crosslinkable group,

Y is the radical —CONHCOO—, —CONHCONH—, —OCONHCO—, —NHCONHCO—, —NHCO—,—CONH—, —NHCONH—, —COO—, —OCO—, —NHCOO— or —OCONH—,

m and p are each independently of the other the number 0 or 1,

R is the residue of a divalent organic compound having from 1 to 20carbon atoms, and

X is the radical —NHCO—, —CONH—, —NHCONH—, —COO—, —OCO—, —NHCOO— or—OCONH—.

P₁ is, for example, alkenyl, which is unsubstituted or substituted, forexample, by C₁-C₄-alkoxycarbonyl or by vinyloxycarbonyl, or alkenylarylor alkenylarylenealkyl, the said radicals each having up to 20 carbonatoms. Examples of alkenyl are vinyl, C₁-C₄alkoxycarbonylvinyl,vinyloxycarbonylvinyl, allyl, 1-propen-2-yl, 1-buten-2-, -3- or -4-yl,2-buten-3-yl and straight-chain or branched pentenyl, hexenyl, octenyl,decenyl and undecenyl. Examples of alkenylaryl are vinylphenyl,vinyinaphthyl and allylphenyl. Examples of alkenylarylenealkyl are o-,m- and p-vinylbenzyl.

P₁ is preferably alkenyl or alkenylaryl each having up to 12 carbonatoms, especially alkenyl having up to 8 carbon atoms and moreespecially alkenyl having up to 4 carbon atoms.

Y is preferably —COO—, —OCO—, —NHCONH—, —NHCOO—, —OCONH—, —NHCO— or—CONH—, especially —COO—, —OCO—, —NHCO— or —CONH— and more especially—COO— or —OCO—.

X is preferably —NHCONH—, —NHCOO— or —OCONH— and especially —NHCOO— or—OCONH—.

The variables m and p are preferably not both the number 0. When p is 0,m is preferably the number 1.

R is preferably alkylene, arylene, cycloalkylene having from 6 to 20carbon atoms, arylene-alkylene, alkylenearylene, alkylenearylenealkyleneor arylenealkylenearylene. R is especially a divalent radical having upto 12 carbon atoms and more especially a divalent radical having up to 8carbon atoms. R is preferably alkylene or arylene having up to 12 carbonatoms, especially alkylene having up to 6 carbon atoms and moreespecially alkylene having up to 4 carbon atoms.

Preferred as radically crosslinkable groups are acryloyl, methacryloyl,maleate, vinyl ether maleate, styryl, acrylamido, methacrylamido,acrylamidoalkyl, urethane methacrylate or unsubstituted or substitutedderivatives of the mentioned radicals, with special preference beinggiven to acryloyl, methacryloyl, acrylamido and methacrylamido.

Especially preferred radically crosslinkable groups correspond toformula (1) above wherein P₁ is alkenyl having up to 4 carbon atoms, Yis —COO— or —CONH—, R is alkylene having up to 4 carbon atoms, X is—NHCOO—, and m and p are each independently of the other 0 or 1, the sumof (m+p) being ≧1.

Cationically crosslinkable groups that may be mentioned are, forexample, epoxy, vinyl ether, propenyl ether, spiroorthoester andspiroorthocarbonate groups and cyclic carbonates, with epoxy or vinylether groups being preferred.

When the cationically crosslinkable group is an epoxy group, that epoxygroup corresponds, for example, to formula

P₂—Y₁—  (2),

wherein

P₂ is the residue of an organic epoxy-group-containing compound and

Y₁ is the radical —NHCO—, —CONH—, —NHCONH—, —COO—, —OCO—, —NHCOO— or—OCONH—.

Examples of suitable residues P₂ correspond to the formula

wherein

R₁ and R₂ are each independently of the other C₁-C₆alkylene.

Y₁ is preferably —COO—, —OCO—, —NHCO— or —CONH—.

Preferred as photocrosslinkable groups are radically polymerisablegroups containing carbon-carbon double bonds, especially acryloyl,methacryloyl, acrylamido or methacrylamido.

A preferred group of prepolymers used according to the inventioncorresponds to the formula

wherein

one of the radicals R₃ and R₄ is hydrogen and the other is methyl, R₅ ishydrogen or C₁-C₃₀-alkyl, n and q are each independently of the other anumber from 0 to 100, the sum of (n+q) being ≧5, and Z is aphotocrosslinkable radical, preferably one of the photocrosslinkableradicals mentioned above, with the said preferences applying. Z informulae (4) and (5) is preferably a radical of formula (1) or (2) aboveand is especially acryloyl, methacryloyl, acrylamido or methacrylamidoor is a radical of formula (2) above wherein Y₁ is —COO—, —OCO—, —CONH—or —NHCO— and P₂ is a residue of formula (3a)-(3d) above.

The prepolymer used according to the invention contains crosslinkablegroups preferably in an amount of from approximately 0.5 toapproximately 80% equivalents, based on the equivalents of monomersforming the polymeric base structure, especially approximately from 1 to50%, more especially approximately from 1 to 25%, preferablyapproximately from 2 to 15% and especially approximately from 3 to 10%.Special preference is given also to amounts of crosslinkable groups offrom approximately 0.5 to approximately 25% equivalents, especiallyapproximately from 1 to 15% and more especially approximately from 2 to12%, based on the equivalents of monomers forming the polymeric basestructure.

The prepolymers used according to the invention are, as mentioned above,crosslinkable but are uncrosslinked or at least substantiallyuncrosslinked.

The average molecular weight of the prepolymers can vary within widelimits, provided that they are liquid or readily meltable andcrosslinkable. An average molecular weight of, for example, from 1000 to50,000 has proved advantageous for the prepolymers used according to theinvention.

In the process according to the invention the prepolymers areadvantageously used in pure form, that is to say free of undesirableconstituents. Undesirable constituents are to be understood in thiscontext as being especially physiologically undesirable constituents,for example monomeric, oligomeric or polymeric starting compounds usedfor the preparation of the prepolymer, or secondary products formedduring the preparation of the prepolymer. The content of thoseundesirable constituents in the prepolymers is preferably ≦0.001% andespecially ≦0.0001% (1 ppm). The prepolymers may, for example as aresult of their synthesis, additionally contain constituents that areacceptable from the physiological stand-point, for example sodiumchloride, such constituents advantageously being present in an amount of≦1%, preferably ≦0.1%, and especially <0.01%.

The prepolymers used in the process according to the invention may, ifnecessary, first be subjected to purification. The purification of theprepolymers can be effected in a manner known per se, for example byprecipitation with organic solvents, such as acetone, filtration andwashing, extraction in a suitable solvent, dialysis or ultrafiltration,with special preference being given to ultrafiltration. By means of thatpurification operation it is possible to obtain the prepolymers in anextremely pure form, for example free or at least substantially free ofreaction products, such as salts, and of starting materials, for examplenon-polymeric constituents.

The preferred process for purifying the prepolymers used in the processaccording to the invention, i.e. ultrafiltration, can be carried out ina manner known per se. It is also possible to carry out suchultrafiltration repeatedly, for example from two to ten times. Theultrafiltration may alternatively be carried out continuously until thedesired degree of purity has been achieved. The degree of purity can inprinciple be as high as desired.

The prepolymers used according to the invention are known per se andsome of them are commercially available or can be obtained in a mannerknown per se from known precursor products, for example by the reactionof the base polymer with a compound containing one of the mentionedphotocrosslinkable groups and a group capable of bonding to the basepolymer, for example a carboxy, carbamoyl, carboxylic acid ester,carboxylic acid anhydride, amino or hydroxy group. Examples of suchcompounds capable of bonding to the base polymer and containing aphotocrosslinkable group are (meth)acrylic acid esters, (meth)acrylamideand derivatives of a cyclohexenoxidecarboxylic acid, for example acorresponding ester or an acid halide.

The liquid or readily meltable prepolymers can be introduced into amould using processes known per se, such as especially conventionalmetering in, for example dropwise introduction. Neither before norduring or after introduction into the mould are solvents, comonomers,for example vinyl comonomers, or further auxiliaries added to theprepolymer or prepolymer mixture, except that a photoinitiator may beadded if appropriate.

Appropriate moulds are manufactured, for example, from polypropylene.Suitable materials for reusable moulds are, for example, quartz,sapphire glass and metals.

When the mouldings to be produced are contact lenses, they can bemanufactured in a manner known per se, for example in a conventional“spin-casting-mold”, as described, for example, in U.S. Pat. No.3,408,429, or in accordance with the so-called full-mold process in astatic mould, as described, for example, in U.S. Pat. No. 4,347,198.

The photocrosslinking can be initiated in the mould, for example byactinic radiation, such as, for example, UV light, or ionisingradiation, such as, for example, gamma radiation or X-rays.

The photocrosslinking is advantageously carried out in the presence of aphotoinitiator capable of initiating, for example, radical or cationiccrosslinking. Examples thereof are familiar to the person skilled in theart; there may be mentioned specifically as suitable radicalphotoinitiators benzoin methyl ether, 1-hydroxycyclohexyl phenyl ketone,Darocure 1173 and Irgacure types and, as cationic photoinitiators,Cyracure types. The photoinitiator is advantageously added to theprepolymers before introduction into the mould, preferably by mixing theprepolymers and the photoinitiator together. The amount ofphotoinitiator can be selected within wide limits, an amount of up to0.05 g/g of prepolymer, and especially up to 0.003 g/g of prepolymer,having proved advantageous.

It should be emphasised that according to the invention the crosslinkingcan be effected in a very short time, for example in <20 minutes,advantageously in ≦10 minutes, preferably in ≦8 minutes, especially in≦5 minutes, more especially in ≦1 minute and especially in ≦30 seconds.

The photocrosslinking is, as already mentioned, carried out in theabsence of solvents, vinyl comonomers or other auxiliaries, with theexception of a photoinitiator which may be present.

The opening of the mould, so that the moulding can be removed from themould, can be carried out in a manner known per se.

A preferred embodiment of the process according to the inventioncomprises the following steps:

a) introducing into a mould, together with a photoinitiator, aprepolymer that is liquid at room temperature or has a melting point of<100° C. and that is substantially free of undesirable constituents, forexample free of monomeric, oligomeric or polymeric starting compoundsused for the preparation of the prepolymer and/or free of secondaryproducts formed during the preparation of the prepolymer, and that issubstantially free of solvents, comonomers and other auxiliaries,

b) initiating the photocrosslinking for a period of ≦5 minutes, and

c) opening the mould, so that the moulding can be removed from themould.

While in processes proposed in the prior art it is generally necessaryfor the removal of the moulding to be followed by purification steps,for example by extraction, such steps are unnecessary in the processaccording to the invention because the prepolymers used do not containundesirable low-molecular-weight constituents; as a result, thecrosslinked product is also free or substantially free of suchconstituents, and subsequent extraction can be omitted. The mouldingsobtainable in accordance with the process of the invention, especiallycontact lenses, are accordingly suitable for their designated usewithout further processing.

The process according to the invention therefore proves to beextraordinarily suitable for the efficient production of a large numberof mouldings, such as contact lenses, within a short time.

Further examples of mouldings that can be produced according to theinvention, in addition to contact lenses, are biomedical and,especially, ophthalmic mouldings, for example intraocular lenses and eyedressings, mouldings for use in surgery, such as heart valves,artificial arteries or the like, and also films or membranes, forexample membranes for controlling diffusion, photostructurable foils forinformation storage, or photoresist materials, for example membranes ormouldings for etching resist or screen printing resist.

When the moulding produced according to the invention is a contact lens,the lens can subsequently be converted into a ready-to-use contact lensin customary manner by hydration. Suitable forms of hydration, in whichready-to-use contact lenses of an extremely varied water content areobtainable, are known to the person skilled in the art. The contact lensis swelled, for example, in water, in an aqueous salt solution,especially in an aqueous salt solution having an osmolarity ofapproximately from 200 to 450 milliosmol in 1000 ml (unit: mosm/l),preferably approximately from 250 to 350 mosm/l and especiallyapproximately 300 mosm/l, or in a mixture of water or an aqueous saltsolution with a physiologically tolerable polar organic solvent, forexample glycerol. The prepolymer is preferably swelled in water or in anaqueous salt solution.

The aqueous salt solutions used for the hydration are advantageouslysolutions of physiologically tolerable salts, such as the buffer saltscustomary in the field of contact lens care, for example phosphatesalts, or the isotonicising agents customary in the field of contactlens care, such as especially alkali metal halides, for example sodiumchloride, or solutions of mixtures thereof. An example of an especiallysuitable salt solution is a synthetic, preferably buffered, lachrymalfluid the pH value and osmolarity of which has been matched to naturallachrymal fluid, for example an unbuffered or, preferably, buffered, forexample phosphate-buffer-buffered, sodium chloride solution, theosmolarity and pH value of which correspond to the osmolarity and pHvalue of human lachrymal fluid.

The hydration fluids defined above are preferably pure, that is to sayfree or substantially free of undesirable constituents. The hydrationfluid is preferably pure water or a synthetic lachrymal fluid asdescribed above.

As already mentioned, the process according to the invention provides anefficient method of producing contact lenses and is at the same timevery versatile both in respect of the conditions for the crosslinkingand in respect of the products obtainable. For example, the crosslinkingcan be effected using various mechanisms, for example radically but alsocationically, and it is also possible to use polymer materials having alow degree of solubility in customary solvents, such as, for example,water, provided that they are swellable in water, and it is possible toproduce ready-to-use contact lenses having either a low water content ora high water content, for example having a water content of >5%.

The contact lenses obtainable in accordance with the process of theinvention also have advantageous properties and in that respect are atleast equivalent to the lenses prepared by previously known processes.Of those properties, mention should be made, for example, of theirexcellent tolerability by the human cornea, which is based on a balanceof water content, oxygen permeability and mechanical properties.Furthermore, the contact lenses according to the invention exhibit ahigh degree of dimensional stability.

In the following Examples, unless expressly indicated to the contrary,amounts are given in amounts by weight and temperatures are given indegrees Celsius. The Examples are not intended to limit the invention inany way, for example to the scope of the Examples.

EXAMPLE 1

1 g of polyethylene glycol-1000-dimethacrylate are mixed with 1.5 mg ofIrgacure®2959 at 40° C. until a clear solution is obtained. A drop ofthe solution is placed between two glass plates having a 100 μ spacerand irradiated for 25 seconds with a Höhnle UV lamp. A clear film isobtained which swells in water. After a swelling time of about 2 hours,the water content of the swelled film is constant and is 40%.

EXAMPLE 2

0.5 g of polyethylene glycol-1000-dimethacrylate and 0.5 g ofpolyethylene glycol monomethacrylate are mixed with 1.5 mg ofIrgacure®2959 at 50° C. until a clear solution is obtained. A drop ofthe solution is placed between two glass plates having a 100 μ spacerand irradiated for 30 seconds with a Höhnle UV lamp. A clear film isobtained which in water yields a hydrogel film having a water content of42%.

EXAMPLE 3

0.5 g of polyethylene glycol-1000-dimethacrylate and 0.5 g of anepoxy-group-containing polyethylene glycol which corresponds to theformula

and in which n=23 are mixed with 20 mg of Cyracure® UVI 6974(triarylsulfonium hexafluoroantimonate UCB) until a clear solution isobtained. A drop of the solution is placed between two glass plateshaving a 100 μ spacer and irradiated for 5 minutes with a Höhnle UVlamp. A clear film is obtained which in water yields a hydrogel filmhaving a water content of about 40%.

What is claimed is:
 1. A process for producing mouldings, comprising thefollowing steps: a) introducing into a mould a prepolymer having aweight average molecular weight of from 1000 to 50000 and containingphotocrosslinkable groups that is liquid at room temperature or isreadily meltable and is substantially free of solvents and comonomers,b) initiating the photocrosslinking for a period of <5 minutes, c)opening the mould, so that the moulding can be removed from the mould.2. A process according to claim 1, wherein the moulding is anophthalmological moulding.
 3. A process according to claim 1, whereinthe polymer base structure of the prepolymer is a polyether, polyester,polyurea, polyurethane, polycarbonate or polyamide or a homogeneousmixture of two or more different mentioned polymers.
 4. A processaccording to claim 1, wherein the polymeric base structure of theprepolymer is a polyether selected from the group consisting of apolyethylene glycol, a polypropylene glycol, a polyethyleneglycol/polypropylene glycol block copolymer and a polytetrahydrofuran.5. A process according to claim 4, wherein the prepolymer corresponds toformula

wherein one of the radicals R₃ and R₄ is hydrogen and the other ismethyl, R₅ is hydrogen or C₁-C₃₀-alkyl, n and q are each independentlyof the other a number from 0 to 100, the sum of (n+q) being ≧5, and Z isa photocrosslinkable group.
 6. A process according to claim 5, whereinthe photocrosslinkable groups correspond to formulaP₁—(Y)_(m)—(R—X)_(p)—  (1) wherein P₁ is a radically crosslinkablegroup, Y is the radical —CONHCOO—, —CONHCONH—, —OCONHCO—, —NHCONHCO—,—NHCO—, —CONH—, —NHCONH—, —COO—, —OCO—, —NHCOO— or —OCONH—, m and p areeach independently of the other the number 0 or 1, R is the residue of adivalent organic compound having from 1 to 20 carbon atoms, and X is theradical —NHCO—, —CONH—, —NHCONH—, —COO—, —OCO—, —NHCOO— or —OCONH—.
 7. Aprocess according to claim 6, wherein P₁ is alkenyl having up to 4carbon atoms, Y is —COO— or —CONH—, R is alkylene having up to 4 carbonatoms, X is —NHCOO— and m and p are each independently of the other 0 or1, the sum of (m+p) being ≧1.
 8. A process according to claim 1, whereinthe photocrosslinkable groups are cationically crosslinkable groupsselected from the group consisting of epoxy, vinyl ether, propenylether, spiroorthoester and spiroorthocarbonate groups and cycliccarbonates.
 9. A process according to claim 1, wherein the prepolymercontaining crosslinkable groups is free or substantially free ofundesirable monomeric, oligomeric or polymeric starting compounds usedfor the preparation of the prepolymer or of secondary products formedduring the preparation of the prepolymer.
 10. A process according toclaim 1, wherein the photocrosslinking is carried out in the presence ofa photoinitiator.
 11. A process according to claim 1, wherein thephotocrosslinking of the prepolymer is carried out in a period of ≦1minute.
 12. A process according to claim 1, wherein extraction to removeundesirable constituents is omitted after the crosslinking.
 13. Aprocess according to claim 1, comprising the following steps: a)introducing into a mould, together with a photoinitiator, a prepolymerthat is liquid at room temperature or has a melting point of <100° C.and that is substantially free of undesirable monomeric, oligomeric orpolymeric starting compounds used for the preparation of the prepolymerand/or free of secondary products formed during the preparation of theprepolymer, and that is substantially free of solvents, comonomers andother auxiliaries, b) initiating the photocrosslinking for a period of≦5 minutes, and c) opening the mould, so that the moulding can beremoved from the mould.
 14. A process for producing a hydrogel, whereina moulding obtained in accordance with claim 1 is subjected to swellingin aqueous solution.
 15. A process according to claim 14, wherein thehydrogel is a contact lens.
 16. A process according to claim 14, whereinthe aqueous solution is a purely aqueous solution or a solution in asynthetic lachrymal fluid.
 17. An ophthalmological moulding obtained bythe process according to claim
 1. 18. A process according to claim 1,wherein the moulding is a contact lens.
 19. A process for producingmouldings, comprising the following steps: a) introducing into a mould aprepolymer and containing photocrosslinkable groups that is liquid atroom temperature or is readily meltable and is substantially free ofsolvents, wherein the photocrosslinkable groups are cationicallycrosslinkable groups selected from the group consisting of epoxy, vinylether, propenyl ether, spiroorthoester and spiroorthocarbonate groupsand cyclic carbonates, b) initiating the photocrosslinking for a periodof <20 minutes, c) opening the mould, so that the moulding can beremoved from the mould.
 20. A process for producing mouldings,comprising the following steps: a) introducing into a mould a prepolymerand containing photocrosslinkable groups that is liquid at roomtemperature or is readily meltable and is substantially free ofsolvents, b) initiating the photocrosslinking for a period of <20minutes, c) opening the mould, so that the moulding can be removed fromthe mould d) swelling the moulding in an aqueous solution selected fromthe group consisting of a purely aqueous solution and a syntheticlachrymal fluid.